Bao Ho

Prospective Comparison of 18F-Fluoromethylcholine Versus 68Ga-PSMA PET/CT in Prostate Cancer Patients Who Have Rising PSA After Curative Treatment and Are Being Considered for Targeted Therapy

In prostate cancer with biochemical failure after therapy, current imaging techniques have a low detection rate at the prostate-specific antigen (PSA) levels at which targeted salvage therapy is effective. 11C-choline and 18F-fluoromethylcholine, though widely used, have poor sensitivity at low PSA levels. 68Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[68Ga-N,N′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid]) has shown promising results in retrospective trials. Our aim was to prospectively compare the detection rates of 68Ga-PSMA versus 18F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatectomy, radiation treatment, or both and were being considered for targeted therapy. Methods: A sample of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. 68Ga-PSMA, 18F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible. Results: In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with 68Ga-PSMA alone, 11 (42%) with both 18F-fluoromethylcholine and 68Ga-PSMA, and only 1 (4%) with 18F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for 68Ga-PSMA versus 12.5% for 18F-fluoromethylcholine. When PSA was 0.5–2.0 ng/mL, the detection rate was 69% for 68Ga-PSMA versus 31% for 18F-fluoromethylcholine, and when PSA was above 2.0, the detection rate was 86% for 68Ga-PSMA versus 57% for 18F-fluoromethylcholine. On lesion-based analysis, 68Ga-PSMA detected more lesions than 18F-fluoromethylcholine (59 vs. 29, P < 0.001). The tumor-to-background ratio in positive scans was higher for 68Ga-PSMA than for 18F-fluoromethylcholine (28.6 for 68Ga-PSMA vs. 9.4 for 18F-fluoromethylcholine, P < 0.001). There was a 63% (24/38 patients) management impact, with 54% (13/24 patients) being due to 68Ga-PSMA imaging alone. Histologic follow-up was available for 9 of 38 patients (24%), and 9 of 9 68Ga-PSMA–positive lesions were consistent with prostate cancer (68Ga-PSMA was true-positive). The lesion positive on 18F-fluoromethylcholine imaging and negative on 68Ga-PSMA imaging was shown at biopsy to be a false-positive 18F-fluoromethylcholine finding (68Ga-PSMA was true-negative). Conclusion: In patients with biochemical failure and a low PSA level, 68Ga-PSMA demonstrated a significantly higher detection rate than 18F-fluoromethylcholine and a high overall impact on management.

68Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment

To examine the detection rates of 68Ga‐PSMA‐positron emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP), and also the impact on their management.

Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer

To assess the accuracy of 68Gallium‐prostate‐specific membrane antigen (68Ga‐PSMA) positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging in intermediate‐ and high‐risk prostate cancer (PCa).

The impact of 68Ga-PSMA PET/CT on management intent in prostate cancer: results of an Australian prospective multicenter study

68Ga-PSMA PET/CT scanning has been shown to be more sensitive than conventional imaging techniques in patients with prostate cancer. This prospective Australian multicenter study assessed whether 68Ga-PSMA PET/CT imaging affects management intent in patients with primary or recurrent prostate cancer. Methods: Before undertaking 68Ga-PSMA PET imaging, referring medical specialists completed a questionnaire detailing relevant demographic and clinical data as well as their proposed management plan. A separate follow-up questionnaire was completed after the 68Ga-PSMA PET/CT scan results were available to determine whether the management plan would change. Results: A total of 431 patients with prostate cancer from 4 Australian centers had pre– and post–68Ga-PSMA management plans completed. Scans were obtained for primary staging of intermediate- and high-risk disease in 25% of patients and for restaging/biochemical recurrence in 75% of patients. Overall, 68Ga-PSMA PET/CT scanning led to a change in planned management in 51% of patients. The impact was greater in the group of patients with biochemical failure after definitive surgery or radiation treatment (62% change in management intent) than in patients undergoing primary staging (21% change). Imaging with 68Ga-PSMA PET/CT revealed unsuspected disease in the prostate bed in 27% of patients, locoregional lymph nodes in 39%, and distant metastatic disease in 16%. Conclusion: 68Ga-PSMA PET/CT scans detect previously unsuspected disease and may influence planned clinical management in a high proportion of patients with prostate cancer. The impact was greater in patients with biochemical recurrence. These results demonstrate the potential clinical value of 68Ga-PSMA PET/CT in management of prostate cancer.

Treatment outcomes from 68GaPSMA PET CT informed salvage radiation treatment in men with rising PSA following radical prostatectomy: Prognostic value of a negative PSMA PET

68Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA ≤ 0.1 ng/mL and >50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% (n = 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6–14 mo). Overall treatment response after SRT was 72% (n = 71/99). Forty-five percent (n = 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% (n = 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% (n = 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% (n = 16/26) had treatment response after SRT. On multivariate logistic regression analysis, PSMA and serum PSA significantly correlated with treatment response, whereas pT stage, Gleason score, and surgical margin status did not. Conclusion: PSMA PET is independently predictive of treatment response to SRT and stratifies men into a high treatment response to SRT (negative or fossa-confined PSMA) versus men with poor response to SRT (nodes or distant-disease PSMA). In particular, a negative PSMA PET result predicts a high response to salvage fossa radiotherapy.

Delineating biochemical failure with 68Ga-PSMA-PET following definitive external beam radiation treatment for prostate cancer

BACKGROUND AND PURPOSE We investigated the role of 68Ga-PSMA-PET (PSMA) to determine the location of disease recurrence in those with a rising PSA following definitive external beam radiation treatment (EBRT). MATERIALS AND METHODS 538men were treated with image guided EBRT to a dose of 78 or 82Gy between 2007 and 2014. Patients at least 24months post EBRT with biochemical failure (nadir+2) underwent PSMA scanning. Local recurrence (LR) was defined as increased uptake within the prostate or seminal vesicles. Distant disease included lymph node (LN), bone or visceral metastases. RESULTS 419men formed the study cohort. Median follow-up was 50months, 70 patients (17%) had biochemical failure (BF), 13 of whom have died. Of the 57 survivors, 5 had metastases detected on conventional scans; 2 were lost to follow up. 48men (of 50 candidates) underwent PSMA; in all cases, the PSMA was unequivocally positive. Of the 48 positive scans, 25 patients (52%) failed beyond the prostate - 5 in bones, 16LN, 3 in both, and 1 in the lungs. Fifteen men (31%) failed within the gland and in either LN (11), bones (3), or both (1). Eight (17%) had an isolated LR, which represents 2% of patients managed with definitive EBRT and followed for at least 2years. CONCLUSIONS PSMA was positive in all patients with BF. Site of failure following dose-escalated EBRT was generally distant. Isolated LR (on PSMA) occurred in only 8 of 419 patients post-EBRT.

68Ga-PSMA-PET/CT staging prior to definitive radiation treatment for prostate cancer

To explore the utility of prostate specific membrane antigen (PSMA)‐positron emission tomography (PET)/computed tomography (CT) in addition to conventional imaging prior to definitive external beam radiation treatment (EBRT) for prostate cancer.

SPECT-CT/VQ versus CTPA for diagnosing pulmonary embolus and other lung pathology: Pre-existing lung disease should not be a contraindication.

Single Photon Emission Computed Tomography‐Ventilation‐Perfusion (SPECT‐VQ) with low‐dose CT (SPECT‐CT/VQ) has equivalent diagnostic accuracy to CTPA for diagnosing pulmonary embolus (PE) while using lower radiation doses, but is underutilized owing to perceived inaccuracy of scintigraphy in the setting of pre‐existing lung disease. This study assesses the accuracy of SPECT‐CT/VQ compared with CTPA for the diagnosis of PE, including in patients with pre‐existing lung disease.

Frusemide aids diagnostic interpretation of 68Ga-PSMA positron emission tomography/CT in men with prostate cancer

68Ga‐PSMA positron emission tomography–computed tomography (PET/CT) is useful for both staging and assessment of biochemical relapse in men with prostate cancer. Renal excretion of 68Ga‐PSMA can lead to difficulties in scan interpretation, particularly in the pelvis. We evaluated if intravenous Frusemide at the time of 68Ga‐PSMA injection reduces excreted activity artefact and improves diagnostic certainty.

Results of a prospective phase 2 pilot trial of Lu177 PSMA 617 therapy for metastatic castrate resistant prostate cancer including Imaging predictors of treatment response and patterns of progression.

Background 177Lu–PSMA‐617 (Lu‐PSMA) is an emerging therapy in men with metastatic castration‐resistant prostate cancer. Paired theranostic agents have the potential to visually identify phenotypes that will respond to targeted therapy. This study examined the value of 68Ga‐HBEDD PSMA‐11; prostate‐specific membrane antigen (PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu‐PSMA therapy within the context of a phase 2 prospective pilot trial. Patients and Methods Men with progressive, symptomatic metastatic castration‐resistant prostate cancer previously treated with antiandrogens (abiraterone and/or enzalutamide) and taxane‐based chemotherapy were prospectively enrolled. Eligibility criteria included uptake on PSMA PET above or equal to liver activity, with no 18F‐Fluoro–deoxyglucose (FDG) PET‐discordant disease. Men received up to 4 cycles of Lu‐PSMA at 6 weekly intervals. Repeat FDG/PSMA PET imaging was performed after completion of therapy or at prostate‐specific antigen (PSA) progression. The study assessed treatment response to Lu‐PSMA using PSA response and correlated treatment response (PSA) to molecular imaging parameters at enrollment. Results Fourteen of 18 men screened underwent Lu‐PSMA therapy. Ten (71%) of 14 had a PSA response (mean reduction, 59%). A ≥ 50% reduction in PSA occurred in 5 (36%), and ≥ 30% in 9 (64%). PSMA PET standardized uptake value (SUV) at screening was predictive of ≥ 30% PSA reduction: SUV max value 17 ± 9 versus 44 ± 15 (P < .007), and PSMA SUV mean 6 ± 4 versus 10 ± 4 (P < .04). FDG parameters alone, and volume or site of disease did not predict PSA response. No imaging parameters predicted ≥ 50% PSA reduction. Nine of 14 men were reimaged after treatment, revealing 3 distinct patterns of progression. Conclusion PSMA PET plays an important role in predicting treatment response to Lu‐PSMA and in identifying subsequent patterns of failure, which may aid in determining the next best treatment options. Micro‐Abstract This study examined the value of 68Ga‐HBEDD (PSMA‐11; prostate‐specific membrane antigen, PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in 177Lu–PSMA‐617 (Lu‐PSMA) therapy within the context of a phase 2 prospective pilot trial. The study found that a minimum intensity of tumor activity is required on PSMA PET to get a treatment response to Lu‐PSMA therapy.